Meta-analysis of diagnostic value of 18F-FDG PET or PET/CT for detecting lymph node and distant metastases in patients with nasopharyngeal carcinoma

Objective:

We performed this meta-analysis to comprehensively assess the diagnostic performance of positron emission tomography (PET) or PET/CT for detecting lymph node and distant metastases in patients with nasopharyngeal carcinoma (NPC).

Methods:

Through a search of four English and three Chinese databases (January 1990 to June 2013), pooled estimated sensitivity, specificity and diagnostic odds ratio (DOR) were calculated based on the data extracted from the included studies. We also constructed summary receiver operating characteristic curves, with the area under the curve (AUC) and obtained the Q* index. Heterogeneity and subgroup analysis were also performed.

Results:

In total, 18 articles consisting 20 studies were included in this meta-analysis. On a per-patient basis, the overall pooled estimates for sensitivity and specificity of PET or PET/CT in N and M staging of NPC were 0.89 [95% confidence interval (CI), 0.86–0.91] and 0.96 (95% CI, 0.95–0.96), respectively. The overall DOR, AUC and Q* index were 162.07 (95% CI, 90.72–289.55), 0.9689 and 0.9181, respectively. Subgroup analysis showed that AUC and Q* index were 0.9734 and 0.9255 for N staging and 0.9715 and 0.9223 for M staging, respectively.

Conclusion:

The present meta-analysis showed that PET or PET/CT has excellent diagnostic performance for detecting lymph node and distant metastases in patients with NPC.

Advances in knowledge:

To provide evidence to assess the role of PET or PET/CT in staging of NPC.In Western countries, nasopharyngeal carcinoma (NPC) is a rare form of squamous cell carcinoma, with incidence rates <1 per 10⁵ persons per year. However, it is a highly frequent epithelial malignancy of the head and neck in southern China and parts of Southeast Asia, with a reported annual incidence of 30–80 per 10⁵ persons in endemic regions, mainly owing to Asian ancestry and infection with the Epstein–Barr virus.^1–3 The mainstay of treatment for nasopharyngeal cancers is using 100 mg m⁻² of cisplatin on Days 1, 22 and 43 concurrent with radiotherapy, followed by adjuvant 80 mg m⁻² of cisplatin on Day 1 and 1000 mg m⁻² of 5-fluorouracil on Days 1–4 for three cycles.^4,5 It is known that stage-adapted therapy significantly improved the survival of patients with cancer.^6,7 In this regard, conventional CT and MRI, mainly providing anatomical information, are performed to assess staging site of NPC, especially for the primary site and local-regional metastases. However, owing to the lack of functional information, these modalities are limited in assessment of disease aggressiveness and distant metastases.⁸ Furthermore, it is difficult to diagnose residual or recurrent NPC owing to the presence of soft-tissue inflammation and oedema after radiotherapy.⁹ In addition, some small volume metastatic nodal lesions may be misinterpreted as reactive nodes when patients show reactive hyperplasia in lymph nodes.Positron emission tomography (PET) and in particular integrated PET/CT using fluorine-18 fludeoxyglucose (¹⁸F-FDG), the latter uniting metabolic function with anatomic form, are widely used techniques in the cancer staging assessment in recent years. Many studies on the staging value of PET or PET/CT for patients with NPC have been performed. For T staging of NPC, PET/CT was less sensitive than MRI, which is plausibly ascribed to the facts that early tumour invasion may have poor ¹⁸F-FDG uptake owing to low tumour burden, while these anatomic areas, including the intracranial area along the cranial nerve, the parapharyngeal space, the skull base and sphenoid sinuses, may be obscured by the spillover effect of ¹⁸F-FDG PET. On the other hand, compared with MRI, partial volume and lack of consensus of optimal strategy for tumour delineation on ¹⁸F-FDG PET may lead to T overstaging. MRI appeared to be superior to PET/CT in delineating primary tumour extent.¹⁰ The use of PET/CT without MRI may lead to inappropriate coverage by radiation portals or improper use of chemotherapy. PET or PET/CT did not have adequate contrast resolution to identity retropharyngeal lymph nodes that merged with adjacent primary tumour or to discriminate direct tumour invasion from metastases, which may result in incorrect N staging or improper use of chemotherapy.¹⁰ However, ¹⁸F-FDG PET/CT may be more accurate than conventional work-up for the determination of neck status and identifying cervical lymph node metastasis, which could facilitate a more appropriate treatment plann, especially for portal designation.^10–12 For those suspicious lymph nodes on conventional imaging or PET/CT, pathological examination may still be necessary. Ultrasound-guided fine-needle aspiration, allowing cytological examination of suspicious nodes as small as 2 mm in diameter, may be a minimally invasive procedure that can enable cytological examination of suspicious lymph nodes.¹³ It has good specificity and a high positive-predictive value but a poor negative-predictive value for identification of metastatic lymph nodes from NPC; furthermore, fine-needle aspiration cytology of the node frequently yields inconclusive results, and this is likely to be related to the increased fibrosis within these nodes after radiation.¹³ With regard to distant metastasis, PET/CT has an acceptable diagnostic yield and a low false-positive rate for the detection of distant malignancy and can replace conventional work-up for this aim.^10,14,15To our knowledge, the results of previous studies are controversial, mainly because of different study design, selection criteria and reference standard. Thus, we performed a meta-analysis of all available studies to comprehensively assess their value in detecting lymph node and distant metastases in patients with NPC.